Online tool for analysis of denaturing gradient gel electrophoresis profiles.
We present an online tool (EquiBands, http://www.univie.ac.at/IECB/limno/equibands/EquiBands.html) that quantifies the matching of two bands considered to be the same in different samples, even when samples are applied to different denaturing gradient gel electrophoresis gels. With an environmental example we demonstrate the procedure for the classification of two bands of different samples with the help of EquiBands.


School racial composition and lifetime non-medical use of prescription painkillers: Evidence from the national longitudinal study of adolescent to adult health.
To investigate the possible effects of middle and high school racial composition on later reporting of lifetime non-medical use of prescription painkillers (NMUPP) in young adulthood, and to explore whether there is evidence of variability by individual race/ethnicity in such effects. Using data from Wave 1 (1994/5) of the National Longitudinal Study of Adolescent to Adult Health (Add Health), we categorized the sample's 52 middle schools and 80 high schools as majority (>50%) non-Hispanic white, majority non-Hispanic black, or neither. We used two-level hierarchical modeling to explore associations between individual- and school-level race at Wave 1 and lifetime prescription painkiller misuse reported at Wave 4. We included a cross-level interaction between individual race and school racial composition to assess variability in school-level associations by race. Overall crude prevalence of lifetime NMUPP in majority white schools (17.9%) was over three times that of prevalence in majority black schools (4.8%), and also higher than prevalence in schools neither predominantly black nor predominantly white (12.4%). Lifetime misuse among blacks in majority white schools was more prevalent (5.2%) than among blacks in black schools (2.8%), as was misuse among whites in white schools (19.3%) compared to their white peers in black schools (15.7%). Two-level random intercept Poisson regression results suggest that attendance in a majority black secondary school lowered a participant's risk of lifetime NMUPP (compared to attending a majority white school: RR=0.66, p = 0.03). Compared to blacks in black schools, blacks in white schools had twice the risk of prescription painkiller misuse (p = 0.004) over a decade later, and whites in white schools had 5.5 times the risk (p = 0.01). The risk ratio comparing whites in black schools to whites in white schools was not significant (RR: 1.30; p = 0.37). We found evidence of an effect of school racial composition on the risk of misusing prescription painkillers over a decade later, over and above individual race, with higher risk of misuse reported among participants who had attended white schools. Black participants who had attended predominantly white schools were, on average, twice as likely to report lifetime misuse of prescription painkillers compared to blacks who had attended black schools.


Evaluation of a novel method for grading heart murmur intensity.
To determine if heart murmur intensity grading performance can be improved using the heart sounds as an internal reference. Single-blind controlled trial of 100 medical students, residents, and pediatric attending physicians at a children's hospital. Groups of 1 to 3 participants were alternately assigned to intervention and control groups, reported their method of grading heart murmur intensity, and then graded the intensity of a random sample of 20 recorded murmurs on a 6-point scale. Before rating another random sample of 20 murmurs, the intervention group was taught a system that uses the heart sounds as an internal reference. Primary outcomes were change in accuracy (percentage correct), interrater agreement (kappa), and consistency (kappa). Subgroup analyses were performed by training level and heart murmur grade. Grading accuracy improved more in the intervention group than the control group (Delta improvement, 5%; 95% confidence interval [CI], -0.1%-10.0%]). This was most pronounced among attending physicians (Delta improvement, 11%; 95% CI, 0.4%-22%) and students (Delta improvement, 12%; 95% CI, 3%-20%) and for grade 2 murmurs (Delta improvement, 20%; 95% CI, 10%-31%). Relatively greater improvements in consistency were observed after the intervention for attending physicians (Delta improvement, 0.17; 95% CI, 0.01-0.32) and grades 2 (Delta improvement, 0.22; 95% CI, 0.09-0.36) and 3 murmurs (Delta improvement, 0.16; 95% CI, 0.05-0.28). A system that uses the heart sounds as an internal reference for grading heart murmur intensity quickly improves accuracy and consistency for some providers and specific murmurs.


Quartz crystal microbalance apparatus for study of viscous liquids at high temperatures.
A design for a Quartz Crystal Microbalance (QCM) setup for use with viscous liquids at temperatures of up to 300 °C is reported. The system response for iron and gold coated QCM crystals to two common lubricant base oils, polyalphaolefin and halocarbon, is reported, yielding results that are consistent with theoretical predictions that incorporate electrode nanoscale surface roughness into their analysis.


[Sphingosine kinase regulates hepatocyte growth factor-induced migration of endothelial cells].
To elucidate the effect of sphingosine kinase (SPK) on the hepatocyte growth factor (HGF)-induced migration of endothelial cells. We constructed recombinant adenoviral vectors, which contain SPK gene and its mutant respectively. These adenoviral vectors were packaged and amplified in 293 cells. And intracellular SPK activity was assayed via measurement of [32]P radioisotope labeled S1P; the effect of SPK activation on HGF-induced migration of endothelial cell was observed by Transwell technique. Adenoviral mediated expression of SPK gene increased in ECV 304 cells intracellular SPK activity, which in turn enhanced the HGF-induced migration. Whereas these activities were blocked by the dominant negative SPK gene. These findings show that SPK activation plays important roles in the regulation of HGF-induced migration of endothelial cells.


A Cytological Study of Oral Human Papillomavirus (HPV) Infection Among Electronic Cigarette Smokers in Al-Madinah Al-Munawara.
Objective This study aims to determine how electronic cigarette (e-cigarette) use contributes to the spread of the human papillomavirus (HPV) and to assess the potential cellular proliferative activity it may produce. Methodology In Madinah, a case-control study was conducted between October 2022 and March 2023. Two oral cytologic smear samples were collected from each of the 500 volunteers; 250 consumers of electronic cigarettes and 250 non-smokers each provided two samples. To detect cytological changes and HPV infection, these samples were stained using Papanicolaou and immunocytochemical techniques. Results Twelve (4.8%) of the electronic cigarettes exhibited cytological atypia, while only one (0.4%) of the nonsmokers' group did. Infection with the human papillomavirus (HPV) was detected in eight (3.2%) of the e-cigarette users, but it was only found in two (0.8%) of the nonsmokers (P ≤ 0.05). Conclusion Electronic cigarette smoking increases the likelihood of contracting HPV and developing cytological atypia, both of which, if left untreated, can contribute to the development of precancerous and cancerous lesions in the mouth.


[A patient with unresectable ampullary carcinoma who underwent subsequent laparoscopic biliary bypass after staging laparoscopy during the same operation].
We report the case of a patient with ampullary carcinoma, diagnosed as having liver metastases by staging laparoscopy, who underwent subsequent laparoscopic biliary bypass during the same operation. A 61-year-old man with jaundice was found to have ampullary carcinoma on CT and ERCP. However, no metastatic lesions were detected on FDG-PET, and we decided to perform laparoscopic pancreaticoduodenectomy. After 1 month of bile drainage and control of cholangitis, we performed a preoperative CT scan that indicated the presence of multiple small low-density areas in the liver. However, it was difficult to distinguish whether the hepatic lesions were metastases or inflammatory changes. Therefore, we decided to choose the operative approach based on the findings obtained from staging laparoscopy. During the procedure, small nodules were observed on the liver surface and were resected. As the resected specimens were found to be adenocarcinomas on pathological examination, we performed Roux-en-Y laparoscopic hepaticojejunostomy using running 4-0 PDS sutures. The postoperative course was uneventful and the patient was discharged on postoperative day 18, after the introduction of systemic chemotherapy. Laparoscopic biliary bypass followed by staging laparoscopy is among the useful methods for unresectable peripancreatic malignancies.


Hiatal hernia, lower esophageal sphincter incompetence, and effectiveness of Nissen fundoplication in the spectrum of gastroesophageal reflux disease.
Gastroesophageal reflux disease (GERD) is a spectrum of disease that includes nonerosive reflux disease (NERD), erosive reflux disease (ERD), and Barrett's esophagus (BE). Treatment outcomes for patients with different stages have differed in many studies. In particular, acid suppressant medication therapy is reported to be less effective for treating patients with NERD and Barrett's esophagus. The aims of this study were to investigate (1) the role of mechanical factors including hiatal hernia and lower esophageal sphincter (LES) competence in the spectrum of GERD and (2) outcomes of Nissen fundoplication. From the records of patients who had undergone laparoscopic Nissen fundoplication after an abnormal pH study, we identified 50 symptomatic consecutive patients with each of the GERD stages: (1) NERD, (2) mild ERD, defined as esophagitis that was healed with acid suppression therapy, (3) severe ERD, defined as esophagitis that persisted despite medical therapy, and (4) BE. Exclusion criteria were normal distal esophageal acid exposure, esophageal pH monitoring performed elsewhere, antireflux surgery less than 1 year previously or previous fundoplication, and a named esophageal motility disorder or distal esophageal low amplitude hypomotility. Patients who could not be contacted for the study were also excluded. All patients completed a detailed preoperative questionnaire; underwent preoperative upper gastrointestinal endoscopy, stationary manometry, and distal esophageal pH monitoring; and were interviewed at least 1 year after operation. One hundred sixty patients meeting the entry criteria were studied. The mean follow-up period was 36.7 months. The only significant preoperative symptom difference was that patients with BE had more moderately severe or severe dysphagia compared to patients with NERD. Patients with severe ERD or BE had a significantly higher prevalence of hiatal hernia, lower LES pressures, and more esophageal acid exposure. Hiatal hernia and hypotensive LES were present in most patients with severe ERD or BE but in only a minority of patients with NERD or mild ERD. Surgical therapy resulted in similarly excellent symptom outcomes for patients in all GERD categories. Compared to mild ERD and NERD, severe ERD and BE are associated with significantly greater loss of the mechanical antireflux barrier as reflected in the presence of hiatal hernia and LES measurements. Restoration of the antireflux barrier and hernia reduction by laparoscopic Nissen fundoplication provides similarly excellent symptom control in all patients.


Gastric Plexiform Fibromyxoma with Two Different Growth Patterns on Histological Images: a Case Report.
Plexiform fibromyxoma (PF) of the stomach is a very rare mesenchymal tumor of the gastrointestinal tract. We report the first case of PF with 2 different growth patterns pathologically confirmed after surgical resection. The tumor was characterized microscopically as infiltrative; it demonstrated diffuse growth into the smooth muscle bundles of the muscularis propria and was also multinodular and plexiform within the myxoid stroma. Immunohistochemical analysis revealed that the tumor cells were positive or weakly positive for smooth muscle actin, vimentin, and H-caldesmon and negative for desmin, CD117, CD34, CK-20, Pan-CK, Dog1, S100, ER, PR, and CD10. No mutations of C-kit and platelet-derived growth factor receptor alpha were detected. No genetic disruption of glioma-associated oncogene homolog 1 was detected by fluorescence in situ hybridization. The final diagnosis of PF was mainly based on the morphological and immunohistochemical findings.


Microinjection of RFRP-1 in the central nucleus of amygdala decreases food intake in the rat.
Several members of the RFamide peptide family are known to have role in the regulation of feeding. For example, neuropeptide FF and prolactin-releasing peptide cause anorexigenic, while 26RFa and QRFP result in orexigenic effects in rodents. I.c.v. microinjection of neuropeptide RFRP-1 significantly reduced food and water intake in chicks. However, feeding related effects of RFRP-1 have not been studied in mammals yet. The central part of amygdala (CeA) is essentially involved in the regulation of feeding and body weight. RFRP-1 positive nerve cells were detected in the rat hypothalamus and RFRP-1 immunoreactive fibers were identified in the CeA. RFRP analogs bind with relatively high affinity to the NPFF1 and NPFF2 receptors (NPFF-R). RFRP-1 has potent activity for NPFF1. Significant expression of NPFF1 was detected in the CeA. To evaluate the role of RFRP-1 in feeding regulation rats were microinjected with different doses of RFRP-1 and their food intake were quantified over a 60min period. Liquid food intake of male Wistar rats was measured after bilateral intraamygdaloid administration of RFRP-1 (25, 50 or 100ng/side, RFRP-1 dissolved in 0.15M sterile NaCl/0.4μl, respectively). The 50ng dose of RFRP-1 microinjections resulted in significant decrease of food intake. The 25 and 100ng had no effect. Action of 50ng (37.8pmol) RFRP-1 was eliminated by 20ng (41.4pmol) RF9 NPFF-R antagonist pretreatment. In open-field test 50ng RFRP-1 did not modify spontaneous locomotor activity and general behavior of animals did not change. Our results are the first reporting that RFRP-1 injected to the CeA result in a decrease of liquid food consumption. This is a receptor-linked effect because it was eliminated by a NPFF-R selective antagonist.


Retention of passive avoidance behavior in rats following alpha- and gamma-endorphin administration: effects of post-learning treatments.
Neuropeptides related to beta-endorphin (beta-LPH61-91) profoundly affect avoidance behavior. That gamma- and alpha-endorphin (beta-LPH61-77 and beta-LPH61-76, respectively) influence memory processes, has been investigated on rats. Using a one-trial learning, step-through passive avoidance paradigm, it was found that gamma-endorphin attenuates later retention of passive avoidance behavior when administered immediately or 3 h after learning; alpha-endorphin facilitates this response when given immediately after learning. Neither gamma- nor alpha-endorphin influence retention when the treatment is postponed for 6 h after learning. These data are interpreted as suggesting an opposite effect of gamma- and alpha-endorphin on consolidation processes.


Effects of interparticle attractions on colloidal sedimentation.
We use a mesoscopic simulation technique to study the effect of short-ranged interparticle attractions on the steady-state sedimentation of colloidal suspensions. Attractions increase the average sedimentation velocity v(s) compared to the pure hard-sphere case, and for strong enough attractions, a nonmonotonic dependence on the packing fraction phi with a maximum velocity at intermediate phi is observed. Attractions also strongly enhance hydrodynamic velocity fluctuations, which show a pronounced maximum size as a function of phi. These phenomena arise from a complex interplay between nonequilibrium hydrodynamic effects and the thermodynamics of transient cluster formation.


Effects of phorbol myristate acetate on interleukin-2 and accompanying interferon production of human leukocytes induced by heat-inactivated Staphylococcus aureus.
Interleukin-2 (IL-2) production induced by heat--inactivated Staphylococcus aureus (SAU) was enhanced by simultaneous addition of phorbol myristate acetate (PMA). The effect was optimal at a concentration of 10 ng/ml SAU; in the presence of 10 ng/ml PMA, the amount of SAU required for maximal IL-2 production was lower. The kinetics of SAU and of SAU plus PMA-induced IL-2 production were similar. Stimulated mononuclear cells produced interferon (IFN) in addition to IL-2. The titre of accompanying IFN was decreased in cultures stimulated with the SAU plus PMA combination. Plastic nonadherent sheep erythrocyte-positive cells were the most active in the SAU-induced IL-2 production. In contrast, the bulk of the IFN activity was produced by the nonadherent E rosette-nonforming cells. Neutralization of IFN with specific antibodies and pH 2 treatment indicated that SAU-induced IFN consisted mainly of alpha-IFN.


Research in physical medicine and rehabilitation. IV. Some practical designs in applied research.
The randomized controlled trial is often difficult, impractical or unethical in the clinical setting. Specific types of experimental design are examined for application and ease of interpretation of results, with particular focus on the generalization and demonstration of cause and effect. Examples are given of relatively easy changes that greatly strengthen the design and several recently published studies are used as illustrative examples.


Long-distance correlations in molecular orientations of liquid water and shape-dependent hydrophobic force.
Liquid water, at ambient conditions, has short-range density correlations which are well known in literature. Surprisingly, large scale molecular-dynamics simulations reveal an unusually long-distance correlation in "longitudinal" part of dipole-dipole orientational correlations. It is nonvanishing even at 75 A and falls off exponentially with a correlation length of about 24 A beyond solvation region. Numerical evidence suggests that the long-range nature of dipole-dipole correlation is due to underlying fluctuating network of hydrogen bonds in the liquid phase. This correlation is shown to give a shape dependant attraction between two hydrophobic surfaces at large distances of separation and the range of this attractive force is in agreement with experiments. In addition it is seen that quadrupolar fluctuations vanish within the first solvation peak (3 A) .


Biomarkers of Barrett's esophagus.
Barrett's esophagus is the strongest risk for esophageal adenocarcinoma (EAC). Metaplasia in patients with BE may progress to dysplasia and then invasive carcinoma. Well-defined diagnostic, progressive, predictive, and prognostic biomarkers are needed to identify the presence of the disease, estimate the risk of malignant transformation, and predict the therapeutic outcome and survival of EAC patients. There are many predictive and prognostic markers that lack substantial validation, and do not allow stratification of patients with gastroesophageal reflux disease in clinical practice for outcome and effectiveness of therapy. In this short review we summarize the current knowledge regarding possible biomarkers, focusing on the pathophysiologic mechanisms to improve prognostic and therapeutic approaches.


Quantitative immunohistochemistry (IHC) analysis of biomarker combinations for human esophageal squamous cell carcinoma.
Esophageal squamous carcinoma (ESCC) is one of the most common cancers in developing countries. However, currently there are no specific biomarkers for ESCC. This study evaluated the expression of proliferating cell nuclear antigen (PCNA), tumor suppressor protein p53, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as biomarkers for ESCC. This study included 60 clinical cases (30 ESCC and 30 non-ESCC cases that were confirmed pathologically). The expression of PCNA, p53, EGFR, and VEGF were investigated using a quantitative computerized immunohistochemistry (IHC) method. The expression level of each protein was indicated by a H-score from the quantitative analysis. Receiver operating characteristic curve (ROC) and area under curve (AUC) analyses were performed. The sensitivity and specificity of each individual protein and combinations of the proteins were calculated. The H-score analysis indicated that expressions of EGFR, PCNA, and VEGF were statistically significantly higher in ESCC than non-ESCC patients; however, p53 was not. The panels of combinations of these proteins were more sensitive than that of any single protein. In the triplicate combination, the AUC prediction probability increased to 0.86, while the single protein AUC prediction probabilities were 0.74 (EGFR), 0.80 (PCNA), and 0.70 (VEGF). The high expression of PCNA, EGFR, and VEGF suggests that they are potential biomarkers for ESCC. The combination of these biomarkers may provide targets for molecular therapy and molecular imaging.


Practical management of hyperthyroidism.
There are several causes of hyperthyroidism, and correct diagnosis is essential for management. Graves' disease is most commonly managed with radioactive iodine therapy (131I), antithyroid drugs or surgery. Toxic adenomas (single or multiple) may be treated with 131I or surgery. Most types of thyroiditis are managed expectantly. Pregnant women, children and the elderly deserve special consideration. Follow-up is vital to identify the later development of hypothyroidism.


Rats as indicators of the presence and dispersal of pathogens in Cyprus: ectoparasites, parasitic helminths, enteric bacteria, and encephalomyocarditis virus.
Rodents play an active role in the transmission of a number of zoonoses by harboring and disseminating the pathogens involved, either through their biological materials or via their ectoparasites. Hence, the spatial and seasonal distribution of potential agents of zoonoses may be studied by examining their distribution in the rodent vectors and their ectoparasites. A surveillance was conducted in wild rodents in 51 different areas of Cyprus, an island ecosystem, to monitor the reemergence of Echinococcus granulosus and Encephalomyocarditis virus (pathogens that have been eradicated from Cyprus), to study the presence and dispersal of Salmonella spp. (a bacterium found in patients and poultry in the island), as well as to investigate the presence of helminth parasites and rodent ectoparasites. Biological material collected from 625 rodents, examined macroscopically, microscopically, and after culture, showed that the most widespread pathogens encountered in wild rats (Rattus rattus and Rattus norvegicus) were helminth parasites, found in 92 animals (three helminth species found for the first time in Cyprus: Cysticercus fasciolaris, Hymenolepis diminuta, and Physalloptera spp.), and Salmonella spp., detected in the intestine of 56 rats (12 different Salmonella spp. and serotypes). None of the rodents were found infected with the cestode Echinococcus or Encephalomyocarditis virus, indicating that the control measures taken by the Veterinary Services on the island prevented its reestablishment despite changing conditions. The rodents were also free of the nematode Trichinella. Over 40% of the rats collected were infested with fleas, mainly Xenopsylla cheopis. The results, analyzed using the Geographical Information System technology, revealed two of the areas studied as high risk for public health.


Papiine herpesvirus 2 as a predictive model for drug sensitivity of Macacine herpesvirus 1 (monkey B virus).
Monkey B virus (Macacine herpesvirus 1; BV) is endemic in macaques. BV (a BSL4 agent) is the primary zoonotic concern for persons working with macaques in research, and human BV infections frequently are fatal. We assessed the use of a BSL2 baboon herpesvirus (Papiine herpesvirus 1; HVP2) for predicting the drug sensitivity of BV by comparing the sensitivity of the 2 viruses to 12 antiherpetic drugs. Plaque reduction assays showed that 4 drugs (HBPG, BVdU, PFA, and BrdU) were ineffective against both viruses. Of the 8 effective drugs, both viruses were most sensitive to TFT, whereas sensitivity to the remaining 7 drugs varied between BV and HVP2 as well as between strains of HVP2. In addition, the efficacy of 5 drugs (ACV, PCV, GCV, CDV, and EDU) was tested by using a murine model. ACV and EDU were completely ineffective against both HVP2 and BV, and high doses of PCV only delayed death by a few days. GCV and CDV both protected mice against death, and CDV also prevented the development of neurologic symptoms. When the initiation of drug therapy was delayed until after virus gained access to the CNS, both GCV and CDV were ineffective. The similarity of the drug sensitivities of HVP2 and BV in both models validates the use of HVP2 as a BSL2 level model that can be used to predict drug sensitivity of BV. The greater efficacy of CDV relative to GCV suggests the potential for use of CDV in the treatment of zoonotic BV infections.


Evaluation and validation of a robust single cell RNA-amplification protocol through transcriptional profiling of enriched lung cancer initiating cells.
Although profiling of RNA in single cells has broadened our understanding of development, cancer biology and mechanisms of disease dissemination, it requires the development of reliable and flexible methods. Here we demonstrate that the EpiStem RNA-Amp™ methodology reproducibly generates microgram amounts of cDNA suitable for RNA-Seq, RT-qPCR arrays and Microarray analysis. Initial experiments compared amplified cDNA generated by three commercial RNA-Amplification protocols (Miltenyi μMACS™ SuperAmp™, NuGEN Ovation® One-Direct System and EpiStem RNA-Amp™) applied to single cell equivalent levels of RNA (25-50 pg) using Affymetrix arrays. The EpiStem RNA-Amp™ kit exhibited the highest sensitivity and was therefore chosen for further testing. A comparison of Affymetrix array data from RNA-Amp™ cDNA generated from single MCF7 and MCF10A cells to reference controls of unamplified cDNA revealed a high degree of concordance. To assess the flexibility of the amplification system single cell RNA-Amp™ cDNA was also analysed using RNA-Seq and high-density qPCR, and showed strong cross-platform correlations. To exemplify the approach we used the system to analyse RNA profiles of small populations of rare cancer initiating cells (CICs) derived from a NSCLC patient-derived xenograft. RNA-Seq analysis was able to identify transcriptional differences in distinct subsets of CIC, with one group potentially enriched for metastasis formation. Pathway analysis revealed that the distinct transcriptional signatures demonstrated in the CIC subpopulations were significantly correlated with published stem-cell and epithelial-mesenchymal transition signatures. The combined results confirm the sensitivity and flexibility of the RNA-Amp™ method and demonstrate the suitability of the approach for identifying clinically relevant signatures in rare, biologically important cell populations.


Strategy to tether organometallic ruthenium-arene anticancer compounds to recombinant human serum albumin.
In order to utilize macromolecules for drug targeting and delivery, a strategy to tether organometallic ruthenium-arene drugs to carrier protein molecules was developed. The approach involves the design of a drug fragment capable of conjugating to linker molecules on a modified carrier protein via hydrazone bond formation. The proof-of-concept using recombinant human serum albumin is described.


Profile of St. Jude Medical's Allure Quadra quadripolar pacemaker system for cardiac resynchronization therapy.
Congestive heart failure is a major public health epidemic and economic burden in the USA and worldwide. Cardiac resynchronization therapy is an effective therapy for treating congestive heart failure in conjunction with pharmacologic therapy. The average congestive heart failure admission costs approximately US$ 8 billion annually. Current cardiac resynchronization therapy pacemaker systems from various manufacturers deliver therapy-utilizing bipolar leads including the left ventricle, with electrode spacing ranging from 8 to 22 mm. The Quartet LV™ lead model 1458Q (St. Jude Medical Sylmar, CA) is a quadripolar lead with a 4.0 Fr. tip electrode and three 4.7 Fr. ring electrodes located 20, 30 and 47 mm from the tip. The Quartet lead and Allure Quadra TM allows 14 pacing configurations, providing benefits, including reductions in phrenic nerve stimulation, reduced pacing thresholds, improved battery longevity and potential reductions, in non-responders to cardiac resynchronization therapy. In addition, there is cost benefit data from utilizing quadripolar technology compared with traditional bipolar cardiac resynchronization therapy.


Effect of dietary supplements of sodium or potassium bicarbonate on short-term macromineral balance in swine.
Four crossbred barrows, weighing an average of 26 kg each, were fitted with simple T-cannulas in the terminal ileum and placed in metabolism cages to evaluate the effect of dietary supplements of NaHCO3 or KHCO3 on the short-term metabolism of sodium (Na), potassium (K), calcium (Ca), magnesium (Mg) and chloride (Cl). A control diet containing 2.8 g/kg Na and 4.1 g/kg K was compared with similar diets supplemented with either 13 g/kg or 26 g/kg NaHCO3 or 30 g/kg KHCO3. All diets contained 4 g/kg Cr2O3 as an external marker and were offered twice daily (1,100 g X pig-1 X d-1) in a 4 X 4 Latin square arrangement. Feces and total urine output were collected for 24 h on the fifth day after introducing a new diet; digesta was collected for 12-h periods on d 6 and 7. Sodium and K concentrations at the terminal ileum were unaffected by dietary treatment. Apparent ileal digestibility of Na was increased by NaHCO3 supplements. Over the total gastrointestinal tract, diet had no affect on apparent Na digestibility. Urinary Na clearance was increased by NaHCO3 in the diet in a dose-dependent manner. Net Na retention (g/d) was increased by NaHCO3. Apparent ileal digestibility of K was increased by KHCO3. Apparent fecal digestibility of K was increased by KHCO3 and NaHCO3. Urinary K clearance was elevated by KHCO3, but not enough to overcome the increased K intake; net K balance (g/d) rose in response to dietary KHCO3 supplements. Sodium bicarbonate or KHCO3 had no effect on short-term digestibility or balance of Mg, Ca or Cl.(ABSTRACT TRUNCATED AT 250 WORDS)


Reconstruction of the resorbed edentulous maxilla using autogenous rib grafts and osseointegrated implants.
14 patients with severely resorbed edentulous maxillae underwent reconstruction by the use of autogenous rib graft on-lays and osseointegrated Brånemark System implants in a one-stage procedure. 75 implants were installed. 16 (21.3%) failed to osseointegrate at the abutment connection. After a mean observation period of 5.2 years, 55 (73.3%) of the original implants were osseointegrated. 10 supplementary implants were inserted in 3 patients. At the end of the observation periods, 2 patients had overdentures and 12 had fixed prostheses. The mean marginal bone loss was 2.13 mm (SD 0.47 mm) the 1st year after grafting, and 2.92 mm (SD 1.27 mm) at the end of the follow-up periods. Long-term follow-up did not show any persistent donor site discomfort. The results indicate that this technique is a conceivable alternative for patients with severe maxillary resorption.


A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray.
Abs are central to malaria immunity, which is only acquired after years of exposure to Plasmodium falciparum (Pf). Despite the enormous worldwide burden of malaria, the targets of protective Abs and the basis of their inefficient acquisition are unknown. Addressing these knowledge gaps could accelerate malaria vaccine development. To this end, we developed a protein microarray containing approximately 23% of the Pf 5,400-protein proteome and used this array to probe plasma from 220 individuals between the ages of 2-10 years and 18-25 years in Mali before and after the 6-month malaria season. Episodes of malaria were detected by passive surveillance over the 8-month study period. Ab reactivity to Pf proteins rose dramatically in children during the malaria season; however, most of this response appeared to be short-lived based on cross-sectional analysis before the malaria season, which revealed only modest incremental increases in Ab reactivity with age. Ab reactivities to 49 Pf proteins measured before the malaria season were significantly higher in 8-10-year-old children who were infected with Pf during the malaria season but did not experience malaria (n = 12) vs. those who experienced malaria (n = 29). This analysis also provided insight into patterns of Ab reactivity against Pf proteins based on the life cycle stage at which proteins are expressed, subcellular location, and other proteomic features. This approach, if validated in larger studies and in other epidemiological settings, could prove to be a useful strategy for better understanding fundamental properties of the human immune response to Pf and for identifying previously undescribed vaccine targets.


Metal-free pincer ligand chemistry polycationic phosphonium Lewis acids.
Oxidation of 2,6-bis(diphenylphosphine)methyl pyridine with MeO3SCF3, yields the dication [2,6-(CH2PMePh2)2C5H3N][CF3SO3]22, while subsequent treatment with two equivalents of [K(THF)n][B(C6F5)4] (n = 1.3-1.5) afforded [2,6-(CH2PMePh2)2C5H3N][B(C6F5)4]23. Analogous treatment using XeF2 afforded 2,6-(CH2PF2Ph2)2C5H3N 4, while subsequent fluoride abstractions afford the corresponding [BF4], [CF3SO3] and [B(C6F5)4] salts, 5-7, respectively. Compound 4 reacts with an excess of MeO3SCF3 to give [2,6-(CH2PF2Ph2)2C5H3N(CH3)][CF3SO3] 8 while subsequent reaction with [Et3Si·2C7H8][B(C6F5)4] gave the related tricationic species, 9. The Lewis acidity of these di- and triphosphonium cations 3, 7 and 9 was examined and their utility as Lewis acid catalysts was assessed in the dimerization of 1,1-diphenylethylene, the hydrodefluorination of 1-fluoroadamantane, and the dehydrocoupling of phenol and silane.


Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient.
We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). Saposin D is distinguished by the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides. The possible reasons for the unique glycosylation of each saposin is discussed.


Effects of floor versus cage rearing and feeder space on growth, long bone development, and duration of tonic immobility in single comb White Leghorn pullets.
The effects of feeder space on growth of commercial layer pullets reared in cages or floor pens were examined by allocating 1-d-old chicks to either cages (14 chicks) or floor (119 chicks). Feeder spaces were 5.4, 4.0, and 2.7 cm per pullet and were held constant throughout the growing period, resulting in a 2 x 3 factorial arrangement. Measurements of pullet body weight, feed consumption, skeletal development, and fearfulness were taken through the rearing period to 18 wk. Pullets allowed 5.4 cm of feeder space were heavier (P < .001) (1,329 g at 18 wk of age) than birds allowed either 4.0 or 2.7 cm of feeder space (1,289 and 1,272 g, respectively). Floor-reared pullets weighed significantly more at 12, 16, and 18 wk of age than cage-reared pullets. Feed consumption was not affected by the feeder space, but the floor-reared birds consumed more (P < .001) feed than those in cages (61.2 vs 52.8 g per pullet per d). Mortality, skeletal development, and bone strength were not affected by either feeder space or floor vs cage rearing. Floor-reared pullets had longer (P < .05) duration of tonic immobility (TI) than those reared in cages (519.7 and 471.4 s, respectively, as measured at 18 wk). Feeder space per pullet had no effect on the duration of TI of the pullets. Cage and floor rearing environments are comparable for rearing pullets provided feeder space is not restricted to such an extent as to inhibit BW.


Body composition and cardiac dimensions in elite rhythmic gymnasts.
Rhythmic gymnasts are often believed to be a population at risk of malnutrition because of their tendency to keep a low weight and a lean appearance for better athletic performance, and because they start intensive training at a very young age. The purpose of this study was to evaluate in adolescent elite gymnasts the effects of physical activity on body composition and cardiac morphology and function. Sixteen national level rhythmic gymnasts and 16 control adolescent female underwent anthropometric measurements, bioelectric impedance and echocardiography to assess body composition and cardiac morphology and function. As compared to controls, gymnasts had lower body mass index (16.9±1.1 vs. 18.7±1.0, P<0.001), fatty mass (14.2±4.5 vs. 15.8±2.9 %, P<0.05) and greater fat-free mass (84.0±4.7 vs. 80.5±5.0 %, P<0.05), left ventricular end-diastolic dimension (4.7±0.4 vs. 4.4±0.3 cm) and left ventricular mass, as absolute (132.8±21.2 vs. 112.5±22.8 g, P<0.01) and indexed (44.5±9.3 vs. 36.1±8.2 g/m2.7, P<0.01). Left ventricular mass was directly related to fat-free mass as absolute (r=0.37, P<0.05) and indexed (r=0.43, P<0.02). Body composition analysis showed a lower percentage of body fat in the gymnasts, together with a higher percentage of fat-free mass. Echocardiographic findings indicate that elite rhythmic gymnastics present left ventricular remodeling as training-induced cardiac adaptation. Intensive training, dietary attitude and evident leanness of rhythmic gymnasts are not associated with cardiac abnormalities, as it is the case of pathological leanness.


Impulsivity: differential relationship to depression and mania in bipolar disorder.
Impulsivity, a component of the initiation of action, may have a central role in the clinical biology of affective disorders. Impulsivity appears clearly to be related to mania. Despite its relationship to suicidal behavior, relationships between impulsivity and depression have been studied less than those with mania. Impulsivity is a complex construct, and it may be related differently to depression and to mania. In subjects with bipolar disorder, we investigated impulsivity in relationship to affective symptoms. Trait-like impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Affective symptoms were measured using the Change version of the Schedule for Affective Disorders and Schizophrenia (SADS-C). Measures were compared using analysis of variance, multiple regression and factor analysis. Impulsivity, as measured by the BIS, was related differentially to measures of depression and mania. Total and attentional impulsivity correlated independently with depression and mania scores. Motor impulsivity correlated with mania scores, while nonplanning impulsivity correlated with depression scores. These relationships were strongest in subjects who had never met criteria for a substance use disorder. Among manic symptoms, visible hyperactivity correlated most strongly with BIS scores, regardless of clinical state. Among depressive symptoms, hopelessness, anhedonia, and suicidality correlated most strongly with BIS scores. Depression and mania are differentially related to impulsivity. Impulsivity is related more strongly to measures of activity or motivation than to depressive or manic affect. The relationship between impulsivity and hopelessness may be an important factor in risk for suicide.


Family therapy approach to addiction.
Family therapy has made a substantial contribution to the prevention of drug addiction. This approach takes fully into account psycho-social relationships in families, particularly in families experiencing addiction, as well as changes in patterns of family life and in social attitudes towards addiction. Drug addiction is a manifestation of serious dysfunctional relationships and interactions in the family and is often interrelated with child and spouse abuse. Such family situations require multidisciplinary therapy measures for which the family, with its network of relationships and behavioural interactions, rather than the individual alone, is regarded as the unit of treatment.


Real-time ultrasound in the detection of intrauterine growth retardation in preeclampsia.
An early identification of eventual intrauterine growth retardation (IUGR) and fetus development using an ultrasound method. Preeclampsia (PIH) complicates from 5 to 10% of pregnancies and it is a leading cause of maternal and fetal mortality and morbidity. The study was conducted during a 2 year period based on patients between 15 and 41 years, divided in two groups: group A based on 67 preeclamptic patients, and group B based on 129 normotensive pregnancises. The fetuses from group A were suspected from IUGR (p<0.05). Based on our study it can be concluded that IUGR is the main complication of the fetus in the hypertensive pregnancy. The most common type of restriction in PIH was the asymmetric type of IUGR. In PIH pregnancies, there could be a faster aging of the placenta and oligohydramnion (Tab. 9, Fig. 7, Ref. 20). Full Text (Free, PDF) www.bmj.sk.


Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.
Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key regulator of inflammation, had significantly reduced consequences from acute P. aeruginosa keratitis. This improvement in the outcome was manifested as improved bacterial clearance, decreased neutrophil infiltration, and decreased inflammatory responses when P. aeruginosa-infected MIF knock out (KO) mice were compared to infected wild-type mice. Recombinant MIF applied to infected corneas restored the susceptibility of MIF deficient mice to P. aeruginosa-induced disease, demonstrating that MIF is necessary and sufficient to cause significant pathology at this immune privileged site. A MIF inhibitor administered during P. aeruginosa-induced infection ameliorated the disease-associated pathology. MIF regulated epithelial cell responses to infection by enhancing synthesis of proinflammatory mediators in response to P. aeruginosa infection and by promoting bacterial invasion of corneal epithelial cells, a correlate of virulence in the keratitis model. Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect.


Changes in glucose tolerance after endoscopic retrograde cholangiopancreatography.
Changes in oral glucose-tolerance have been studied in patients subjected to endoscopic retrograde pancreatography. Glucose tolerance is impaired 72 hours after ductography, and significant changes can still be seen even after one month; glucose tolerance returns to normal six to 12 months after pancreatography. In an attempt to discover the mechanism underlying impaired tolerance serial measurements were made of plasma insulin and glucagon levels. The observation that the ratio I/G decreased in these patients indicates that enhanced glucagon release, probably due to mechanical and/or osmotic injury, may be responsible for the hyperglycaemia that is observed.


Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies.
Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon regeneration of peripheral nerves, where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers. Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632. Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity. In contrast, the same dose showed toxic effects on the regeneration of myelinated fibers. Interestingly, scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632. Overall, these findings confirm the in vivo participation of RhoA/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody. Our findings open the possibility of therapeutic pharmacological intervention targeting RhoA/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.


An ethnic comparison of eating attitudes and associated psychological problems in young British women.
The study aimed to investigate possible differences in eating attitudes/problems and associated psychological problems in young women of differing ethnic origin. In a city with a relatively high Asian population (with a background in the Indian subcontinent), 235 young women aged 18-27 registered with a general practice responded to a postal questionnaire. The questionnaire examined eating and weight problems (including the 26-item Eating Attitudes Test), self-esteem (measured by the Rosenberg Self-Esteem Scale), and general psychological well-being (measured by The Hospital Anxiety and Depression Scale). We also included three short vignettes designed to assess illness perception and health seeking-behavior. We found relatively little difference in eating attitudes and problems according to ethnicity, although self-induced vomiting for weight control was more common among Caucasian women. Neither was there any difference in self-esteem, anxiety, depression, and illness perception. The results suggest that one cannot generalize about eating problems across the Asian population and a more sophisticated approach to the examination of sociocultural factors is recommended.


Methods for measurement of root canal curvature: a systematic and critical review.
The assessment of root canal curvature is essential for clinical and research purposes. This systematic review presents an overview of the published techniques for the measurement of root canal curvature features using imaging and to provide a critique of their clinical application. A database search in PubMed, PubMed Central, Embase, Scopus, EBSCO Dentistry & Oral Sciences Source and Virtual Health Library was conducted, using appropriate key words to identify measurement methods for root canal curvatures. The search strategy retrieved 10594 records in total, and 31 records fulfilled the inclusion criteria. From 2D image acquisitions, eleven studies measured exclusively the angle of curvature, an additional thirteen measured other curvature features (level, height, radius, length and shape). Seven reports described methods from 3D imaging (CBCT, μCT). Root canal curvatures should be measured, for clinical proposes, to facilitate endodontic treatment planning, and in research, to reduce the risk of selection bias. This review has revealed that there are many methods described in the literature; however, no consensus exists on which method should be used. Some of the methodologies have potential clinical translation, whereas others are suitable for research purpose only, as they require a specific software or radiographic exposure in the mesiodistal direction.


Recent Advances in the Pathogenesis and Clinical Evaluation of Portal Hypertension in Chronic Liver Disease.
In chronic liver disease, hepatic stellate cell activation and degeneration of liver sinusoidal endothelial cells lead to structural changes, which are secondary to fibrosis and the presence of regenerative nodules in the sinusoids, and to functional changes, which are related to vasoconstriction. The combination of such changes increases intrahepatic vascular resistance and causes portal hypertension. The subsequent increase in splanchnic and systemic hyperdynamic circulation further increases the portal blood flow, thereby exacerbating portal hypertension. In clinical practice, the hepatic venous pressure gradient is the gold-standard measure of portal hypertension; a value of ≥10 mm Hg is defined as clinically significant portal hypertension, which is severe and is associated with the risk of liver-related events. Hepatic venous pressure gradient measurement is somewhat invasive, so evidence on the utility of risk stratification by elastography and serum biomarkers is needed. The various stages of cirrhosis are associated with different outcomes. In viral hepatitis-related cirrhosis, viral suppression or elimination by nucleos(t)ide analog or direct-acting antivirals results in recompensation of liver function and portal pressure. However, careful follow-up should be continued, because some cases have residual clinically significant portal hypertension even after achieving sustained virologic response. In this study, we reviewed the current and future prospects for portal hypertension.


[Metamphetamine-related disorders: Diagnostics and therapy].
In recent years, mental and behavioral disorders caused by methamphetamine - crystal meth - have increased sharply in Germany. This mainly affects federal states near the border with the Czech Republic. But also nationally, the importance of the drug is increasing, especially in chemsex scenes. The article provides knowledge of methamphetamine, the associated disorders, and provides up-to-date recommendations for diagnostics and treatment based on recent guidelines.


Multisoftware reproducibility study of stress and rest myocardial blood flow assessed with 3D dynamic PET/CT and a 1-tissue-compartment model of 82Rb kinetics.
Routine quantification of myocardial blood flow (MBF) requires robust and reproducible processing of dynamic image series. The goal of this study was to evaluate the reproducibility of 3 highly automated software programs commonly used for absolute MBF and flow reserve (stress/rest MBF) assessment with (82)Rb PET imaging. Dynamic rest and stress (82)Rb PET scans were selected in 30 sequential patient studies performed at 3 separate institutions using 3 different 3-dimensional PET/CT scanners. All 90 scans were processed with 3 different MBF quantification programs, using the same 1-tissue-compartment model. Global (left ventricle) and regional (left anterior descending, left circumflex, and right coronary arteries) MBF and flow reserve were compared among programs using correlation and Bland-Altman analyses. All scans were processed successfully by the 3 programs, with minimal operator interactions. Global and regional correlations of MBF and flow reserve all had an R(2) of at least 0.92. There was no significant difference in flow values at rest (P = 0.68), stress (P = 0.14), or reserve (P = 0.35) among the 3 programs. Bland-Altman coefficients of reproducibility (1.96 × SD) averaged 0.26 for MBF and 0.29 for flow reserve differences among programs. Average pairwise differences were all less than 10%, indicating good reproducibility for MBF quantification. Global and regional SD from the line of perfect agreement averaged 0.15 and 0.17 mL/min/g, respectively, for MBF, compared with 0.22 and 0.26, respectively, for flow reserve. The 1-tissue-compartment model of (82)Rb tracer kinetics is a reproducible method for quantification of MBF and flow reserve with 3-dimensional PET/CT imaging.


Contemporaneous acute myeloid leukaemia and sarcoidosis. Report of three cases.
Three cases of contemporaneous acute myeloid leukaemia (AML) and sarcoidosis are described. The possible pathogenic mechanisms concerning their concurrent appearance are discussed: if sarcoidosis impaired T-cell response, it could perhaps predispose the development of AML; alternatively, the development of sarcoidosis during AML may be due to a reaction linked to a diffuse release of tumour antigens with a subsequent formation of a non-caseating granulomata.


Near-infrared to near-infrared upconverting NaYF4:Yb3+,Tm3+ nanoparticles-aptamer-Au nanorods light resonance energy transfer system for the detection of mercuric(II) ions in solution.
A new luminescence resonant energy transfer (LRET) system has been designed that utilizes near-infrared (NIR)-to-NIR upconversion lanthanide nanophosphors (UCNPs) as the donor, and Au nanorods (Au NRs) as the acceptor. The UCNPs were excited by a near-infrared (980 nm) wavelength and also emitted at a near-infrared wavelength (804 nm) using an inexpensive infrared continuous wave laser diode. The Au NRs showed a high absorption band around 806 nm, which provided large spectral overlap between the donor and the acceptor. Hg(2+) ions were added to an aqueous solution containing the UCNPs and Au NRs that were modified with a Hg(2+) aptamer. Then, a sandwich-type LRET system was developed for the detection of Hg(2+) ions that had high sensitivity and selectivity in the NIR region. The method was successfully applied to the sensing of Hg(2+) ions in water and human serum samples.


KDM4B-mediated epigenetic silencing of miRNA-615-5p augments RAB24 to facilitate malignancy of hepatoma cells.
Emerging evidence indicates that dysregulation of microRNAs (miRNAs) contributes to hepatocellular carcinoma (HCC) tumorigenesis and development. Here, we found that miR-615-5p was obviously downregulated in HCC. Furthermore, the deficiency of demethylase KDM4B stimulated the CpG methylation of miR-615-5p promoter and then decreased the miR-615-5p expression. The Ras-related protein RAB24 was found to be downregulated by miR-615-5p. The low level of miR-615-5p increased the expression of RAB24 and facilitated HCC growth and metastasis in vitro and in vivo. Moreover, miR-615-5p suppresses HCC cell growth by influencing cell cycle progression and apoptosis. Downregulation of miR-615-5p and upregulation of RAB24 promotes the epithelial-mesenchymal transition (EMT), adhesion and vasculogenic mimicry (VM) of HCC cells, all of which contribute to cell motility and metastasis. Thus, miR-615-5p, who is downregulated by KDM4B-mediated hypermethylation in its promoter, functions as a tumor suppressor by inhibiting RAB24 expression in HCC. In conclusion, our findings characterize miR-615-5p as an important epigenetically silenced miRNA involved in the Rab-Ras pathway in hepatocellular carcinoma and expand our understanding of the molecular mechanism underlying hepatocarcinogenesis and metastasis.


Validation of a Custom Instrumented Retainer Form Factor for Measuring Linear and Angular Head Impact Kinematics.
Head impact exposure in popular contact sports is not well understood, especially in the youth population, despite recent advances in impact-sensing technology which has allowed widespread collection of real-time head impact data. Previous studies indicate that a custom-instrumented mouthpiece is a superior method for collecting accurate head acceleration data. The objective of this study was to evaluate the efficacy of mounting a sensor device inside an acrylic retainer form factor to measure six-degrees-of-freedom (6DOF) head kinematic response. This study compares 6DOF mouthpiece kinematics at the head center of gravity (CG) to kinematics measured by an anthropomorphic test device (ATD). This study found that when instrumentation is mounted in the rigid retainer form factor, there is good coupling with the upper dentition and highly accurate kinematic results compared to the ATD. Peak head kinematics were correlated with r2 > 0.98 for both rotational velocity and linear acceleration and r2 = 0.93 for rotational acceleration. These results indicate that a rigid retainer-based form factor is an accurate and promising method of collecting head impact data. This device can be used to study head impacts in helmeted contact sports such as football, hockey, and lacrosse as well as nonhelmeted sports such as soccer and basketball. Understanding the magnitude and frequency of impacts sustained in various sports using an accurate head impact sensor, such as the one presented in this study, will improve our understanding of head impact exposure and sports-related concussion.


A novel SP1/SP3 dependent intronic enhancer governing transcription of the UCP3 gene in brown adipocytes.
Uncoupling protein (UCP) 3 is a mitochondrial inner membrane protein implicated in lipid handling and metabolism of reactive oxygen species. Its transcription is mainly regulated by peroxisome proliferator-activated receptors (PPAR), a family of nuclear hormone receptors. Employing bandshift assays, RNA interference and reporter gene assays we examine an intronic region in the UCP3 gene harboring a cis-element essential for expression in brown adipocytes. We demonstrate binding of SP1 and SP3 to this element which is adjacent to a direct repeat 1 element mediating activation of UCP3 expression by PPARγ agonists. Transactivation mediated by these elements is interdependent and indispensable for UCP3 expression. Systematic deletion uncovered a third binding element, a putative NF1 site, in close proximity to the SP1/3 and PPARγ binding elements. Data mining demonstrated binding of MyoD and Myogenin to this third element in C2C12 cells, and, furthermore, revealed recruitment of p300. Taken together, this intronic region is the main enhancer driving UCP3 expression with SP1/3 and PPARγ as the core factors required for expression.


Learning navigation - Learning with navigation. A review.
The goal of this review paper is to retrieve from the existing literature relevant information (1) about the learning curve of the currently existing navigation systems and (2) about the use of navigation system for teaching orthopaedic procedures. All studies reporting on the learning curve of navigation systems support the hypothesis that computer-navigated total knee arthroplasty (TKA) involves only a short learning curve and that beginners can obtain good results from the beginning of their experience, as navigation provides continuous feedback during all phases of the knee replacement surgery and allows for correcting any bone cut errors. Interestingly, there is no comparable research on the learning curve of TKA with standard, manual instrumentation. One might postulate that this learning curve might be longer than with navigation, with potentially a higher rate of outliers. The current literature does support that navigation may be an efficient teaching tool for both experienced orthopaedic surgeons and trainees. Experienced surgeons may improve their skills with conventional techniques and learn new techniques more efficiently and more quickly. Trainees may have a better understanding of the procedure and learn standard techniques with a shorter learning curve. This is probably due to the immediate feedback of navigation systems. A shorter learning curve may be associated with improved clinical and functional results for the patient during this critical period. However, there is no evidence that training with navigation excludes trainees from the need to work in academic environments with experienced teachers. Future techniques in training may include the development of laboratory simulation procedures using navigated feedback.


Safety and Tolerability of a Rapid Transition From Intravenous Treprostinil to Oral Selexipag in Three Adolescent Patients With Pulmonary Arterial Hypertension.
There is limited published experience with transitioning pediatric patients from parenteral treprostinil to oral selexipag therapy. In addition, published transitions have typically been protracted, taking several weeks to complete. We present a case series of 3 adolescent patients who were transitioned from parenteral treprostinil to oral selexipag over a 5- to 7-day period. Their clinical courses leading up to the transitions are summarized and their outcomes are described. The 3 patients were successfully rapidly transitioned during an inpatient hospitalization without any observed adverse events or prostacyclin-related side effects. We conclude that when indicated rapid transition of parenteral to oral prostacyclin therapy may be performed safely in adolescents in an inpatient setting.


Low day 3 luteinizing hormone values are predictive of reduced response to ovarian stimulation.
The aim of the present work was to evaluate whether low day 3 luteinizing hormone (LH) values in the presence of normal follicle stimulating hormone (FSH) are predictive of poor response to ovarian stimulation. Two groups of women undergoing ovarian stimulation and differing only in the day 3 LH concentration (<3 mIU/ml, study group, n=30; >3 mIU/ml, control group, n=45) were retrospectively analysed. Study group patients developed a lower oestradiol peak (703+/-388 versus 955+/-400 ng/ml; P = 0.005) and a lower number of follicles >15 mm diameter at the time of human chorionic gonadotrophin (HCG) administration (2.6+/-1.3 versus 3.6+/-1.8; P=0.004) than the control group. Conversely, a similar ratio of oestradiol: follicles >15 mm diameter was observed (256+/-118 versus 269+/-93; P=0.563). The number of follicles >10 mm at the time of HCG administration appeared to be lower in the study group, but this difference was not statistically significant (6+/-3.9 versus 7.8+/-4.3). Our data indicate that day 3 LH values <3 mIU/ml are predictive of poor response to ovarian stimulation.


Race, Age, and Geography Impact Hepatitis C Genotype Distribution in the United States.
To determine the impact of geography and patient characteristics on hepatitis C virus (HCV) genotype and subtype distribution in a large sample of patients under routine clinical care BACKGROUND:: HCV genotype impacts disease course and response to treatment. Although several studies have reported genotype distribution within specific US populations, there are no comprehensive descriptions in large, geographically diverse cohorts. Using data from the Chronic Hepatitis Cohort Study, we present the distribution of HCV genotypes (GT) and subtypes (ST) among a racially diverse cohort of over 8000 HCV-infected patients from four large US health systems. Genotype distribution varied significantly by geographic and demographic factors. In age-adjusted analyses, African American patients had significantly higher prevalence of GT1 (85%) than other racial categories, largely driven by a markedly higher proportion of GT1 subtype b (∼34%) than in Asian/other (24%) and white (21%) patients. GT3 represented an increasing proportion of infections as birth decade progressed, from 4% in patients born before 1946 to 18% of those born after 1976. Within the cohort of "living/uncured" patients, highly elevated alanine aminotransferase (>2 times the upper limit of normal) was significantly more common in GT3 patients, whereas Fibrosis-4 Index scores indicative of cirrhosis were most common in the combined group of GT4&6 patients. Distribution of HCV genotypes and subtypes in the United States is more variable than suggested by previous national-level estimates and single-center studies. "Real-world" prevalence data may improve targeting of prevention, screening, and treatment efforts for hepatitis C.


The joint effects of ADH1B variants and childhood adversity on alcohol related phenotypes in African-American and European-American women and men.
The ADH1B gene has consistently been implicated in problem drinking, but rarely incorporated into gene by environment investigations of alcohol phenotypes. This study examined the joint effects of variation in ADH1B and childhood adversity-a well-documented risk factor for alcohol problems and moderator of genetic liability to psychiatric outcomes-on maximum drinks consumed in a 24-hour period (maxdrinks) and alcohol use disorder (AUD) symptoms. Data were drawn from 2,617 African-American (AA) and 1,436 European-American (EA) participants (42% female) in a multisite genetic study of substance dependence. We tested the most significant ADH1B single nucleotide polymorphisms for alcohol dependence from a genomewide association study with this sample, ADH1B-rs1229984 (Arg48His) and ADH1B-rs2066702 (Arg370Cys), in EA and AA subsamples, respectively. Ordinal regression analyses conducted separately by sex and population revealed significant main effects for childhood adversity for both alcohol phenotypes in AA women and men and for maxdrinks in EA women. A significant rs1229984 by childhood adversity interaction was observed for AUD symptoms in EA men. Unexposed His-allele carriers reported a mean of 3.6 AUD criteria, but adversity-exposed His-allele carriers endorsed approximately the same number (6.3) as those without the protective allele (6.3 and 7.0 for adversity-exposed and -unexposed groups, respectively). Results suggest that under conditions of childhood adversity, the His allele does not exert its protective effects in EA men (OR = 0.57, CI: 0.32 to 1.01; p = 0.056). Findings highlight the robust risk effect conferred by childhood adversity and the importance of considering population and sex in genetically informative investigations of its association with alcohol outcomes.


JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region.
JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215bp) and IG (610bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4(+)/TCD8(+) lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.


Stage I vitamin D-deficiency rickets mimicking pseudohypoparathyroidism type II.
The clinical presentation and biochemical features of stage I vitamin D-deficiency rickets (VDR) and pseudohypoparathyroidism (PHP) type II are quite similar. These 2 entities have therefore often been mistaken for one another. We report our experience with 2 cases of stage I VDR that were originally diagnosed as PHP type II. The report provides an insight into the pathophysiology of VDR and PHP and thus allows for better differentiation between the 2 disease entities. It has become essential for pediatricians to recognize VDR owing to its resurgence in developed countries.


Mutant TP53 posttranslational modifications: challenges and opportunities.
The wild-type (WT) human p53 (TP53) tumor suppressor can be posttranslationally modified at over 60 of its 393 residues. These modifications contribute to changes in TP53 stability and in its activity as a transcription factor in response to a wide variety of intrinsic and extrinsic stresses in part through regulation of protein-protein and protein-DNA interactions. The TP53 gene frequently is mutated in cancers, and in contrast to most other tumor suppressors, the mutations are mostly missense often resulting in the accumulation of mutant (MUT) protein, which may have novel or altered functions. Most MUT TP53s can be posttranslationally modified at the same residues as in WT TP53. Strikingly, however, codons for modified residues are rarely mutated in human tumors, suggesting that TP53 modifications are not essential for tumor suppression activity. Nevertheless, these modifications might alter MUT TP53 activity and contribute to a gain-of-function leading to increased metastasis and tumor progression. Furthermore, many of the signal transduction pathways that result in TP53 modifications are altered or disrupted in cancers. Understanding the signaling pathways that result in TP53 modification and the functions of these modifications in both WT TP53 and its many MUT forms may contribute to more effective cancer therapies.


Simulating lateral distraction osteogenesis.
Distraction osteogenesis is an effective method for generating large amounts of bone in situ for treating pathologies such as large bone defects or skeletal malformations, for instance leg-length discrepancies. While an optimized distraction procedure might have the potential to reduce the rate of complications significantly, our knowledge of the underlying mechanobiological processes is still insufficient for systematic optimization of treatment parameters such as distraction rate or fixation stiffness. We present a novel numerical model of lateral distraction osteogenesis, based on a mechanically well-controlled in vivo experiment. This model extends an existing numerical model of callus healing with viscoplastic material properties for describing stress relaxation and stimuli history-dependent tissue differentiation, incorporating delay and memory effects. A reformulation of appositional growth based non-local biological stimuli in terms of spatial convolution as well as remeshing and solution-mapping procedures allow the model to cope with severe mesh distortions associated with large plastic deformations. With these enhancements, our model is capable of replicating the in vivo observations for lateral distraction osteogenesis in sheep using the same differentiation rules and the same set of parameters that successfully describes callus healing in sheep, indicating that tissue differentiation hypotheses originally developed for fracture healing scenarios might indeed be applicable to distraction as well. The response of the model to modified distraction parameters corresponds to existing studies, although the currently available data is insufficient for rigorous validation. As such, this study provides a first step towards developing models that can serve as tools for identifying both interesting research questions and, eventually, even optimizing clinical procedures once better data for calibration and validation becomes available.


Bumblebees can discriminate between scent-marks deposited by conspecifics.
Bumblebees secrete a substance from their tarsi wherever they land, which can be detected by conspecifics. These secretions are referred to as scent-marks, which bumblebees are able to use as social cues. Although it has been found that bumblebees can detect and associate scent-marks with rewarding or unrewarding flowers, their ability at discriminating between scent-marks from bumblebees of differing relatedness is unknown. We performed three separate experiments with bumblebees (Bombus terrestris), where they were repeatedly exposed to rewarding and unrewarding artificial flowers simultaneously. Each flower type carried scent-marks from conspecifics of differing relatedness or were unmarked. We found that bumblebees are able to distinguish between 1. Unmarked flowers and flowers that they themselves had scent-marked, 2. Flowers scent-marked by themselves and flowers scent-marked by others in their nest (nestmates), and 3. Flowers scent-marked by their nestmates and flowers scent-marked by non-nestmates. The bumblebees found it more difficult to discriminate between each of the flower types when both flower types were scent-marked. Our findings show that bumblebees have the ability to discriminate between scent-marks of conspecifics, which are potentially very similar in their chemical composition, and they can use this ability to improve their foraging success.


Massive Intraabdominal Relapse in a Patient with Acute Lymphocytic Leukemia.
Abdominal involvement in an isolated extramedullary relapse region in patients with acute lymphocytic leukemia (ALL) is a rare event, especially in patients in hematological remission. The literature related to this subject is very limited. In this study, a 23-year-old male patient, is presented who had been in remission for 4 years, was admitted because of an enlarged testis, and was found to have an abdominal bulky mass during physical examination. An early diagnosis of abdominal involvement is extremely important and must be kept in mind for ALL patients who are admitted for testicular relapse.


Immunocytochemical distribution of corticotropin (ACTH) in monkey brain.
The distribution of adrenocorticotropin (ACTH) in monkey brain was examined by immunoperoxidase immunohistochemistry. An antiserum to ACTH that recognized the C-terminal portion of the molecule was used. Immunoreactive ACTH was visualized as an intraneuronal constituent with a widespread distribution throughout the brain. Reactive cell bodies were seen only in the region of the arcuate nucleus of the hypothalamus. Dense axonal networks were seen in the hypothalamus, mesencephalic gray, and in the region around the anterior commissure. No staining was seen in the cerebral cortex, cerebellum, hippocampus, or striatum. ACTH or fragments of ACTH may function as neurotransmitters or neuromodulators in primate brain.


Prognostic significance of immunologic changes in 675 infants perinatally exposed to human immunodeficiency virus. The Italian Register for Human Immunodeficiency Virus Infection in Children.
Neutrophil, lymphocyte, and T-cell subset numbers and immunoglobulin levels were evaluated at birth to age 2 years in 675 children born to mothers infected with the human immunodeficiency virus type 1 (58 infected symptom-free subjects (P-1), 203 infected subjects with symptoms (P-2), and 414 uninfected subjects). The P-2 patients had (even at birth to age 1 month) lower CD4+ lymphocyte and higher IgA and IgM values than P-1 and uninfected children had. Increased IgG values (from 1 to 6 months of age) and increased CD8+ lymphocyte numbers (at 13 to 24 months of age) were also observed. The P-1 children differed from uninfected children only at 13 to 24 months of age (decreased CD4+ and increased CD8+ lymphocytes). Progressive immunologic changes were found in P-2 patients who had severe clinical conditions and in those who died. To evaluate the predictive meaning of the immunologic changes, we selected 164 children (25 P-2, 15 P-1, and 124 uninfected children) because they had been examined sequentially from birth and they were classified as in the indeterminate state of infection (P-0) at immunologic evaluations at birth to age 1 and at 1 to 6 months of age. During the 1- to 6-month period, P-2 patients had higher immunoglobulin and lower CD4+ lymphocyte values than P-1 and uninfected children had; no difference was found between P-1 and uninfected subjects. These results indicate that in infants with perinatal human immunodeficiency virus type 1 infection, immunologic abnormalities correlate with the clinical condition and are predictive of the clinical outcome rather than the infection status.


Apolipoprotein B metabolism: tracer kinetics, models, and metabolic studies.
The study of apolipoprotein (apo) B metabolism is central to our understanding of lipoprotein metabolism. However, the assembly and secretion of apoB-containing lipoproteins is a complex process. Specialized techniques, developed and applied to in vitro and in vivo studies of apoB metabolism, have provided insights into the mechanisms involved in the regulation of this process. Moreover, these studies have important implications for understanding both the pathophysiology as well as the therapeutic options for the dyslipidemias. The purpose of this review is to examine the role of apoB in lipoprotein metabolism and to explore the applications of kinetic analysis and multicompartmental modeling to the study of apoB metabolism. New developments and significant advances over the last decade are discussed.


Do colonic short-chain fatty acids contribute to the long-term adaptation of blood lipids in subjects with type 2 diabetes consuming a high-fiber diet?
We recently obtained evidence of long-term adaptation of blood lipids to changes in intakes of carbohydrate and fiber in subjects with type 2 diabetes. We determined the effect of increased carbohydrate and fiber intakes on serum short-chain fatty acids (SCFAs) and the relation between changes in serum acetate and changes in blood lipids. Subjects with type 2 diabetes (n = 62) were randomly assigned to receive approximately 10% of energy from low-fiber breakfast cereal (LF diet), high-fiber breakfast cereal (HF diet), or monounsaturated fatty acids (MUFA diet) for 6 mo. Carbohydrate intakes were higher in the LF and HF groups than in the MUFA group (54% compared with 43%), and more fiber was consumed by the HF group (approximately 50 g/d) than by the LF or MUFA group (approximately 23 g/d). Fasting serum SCFAs did not change significantly over the first 3 mo. Between 3 and 6 mo, serum acetate tended (NS) to decrease in the LF group (from 69 +/- 4 to 59 +/- 5 micromol/L) and increase in the HF group (from 100 +/- 18 to 107 +/- 17 micromol/L), with no significant change in the MUFA group. Serum butyrate did not change significantly in the LF or MUFA group but increased in the HF group (from 2.5 +/- 0.5 to 3.1 +/- 0.6 micromol/L; P < 0.001). Changes in serum acetate from 0 to 3 mo were not related to changes in lipids. However, changes in serum acetate from 3 to 6 mo were positively related to changes in the ratio of total to HDL cholesterol (P = 0.041) and in fasting (P = 0.013) and postprandial (P = 0.016) triacylglycerols. In subjects with type 2 diabetes, changes in serum SCFAs in response to changes in carbohydrate and fiber intakes took many months to occur, and the changes in serum acetate were significantly related to the long-term adaptive changes in blood lipids.


Host Resistance to Virus Diseases Provides a Key Enabler towards Fast Tracking Gains in Grain Lupin Breeding.
Four lupin species, Lupinus angustifolius, L. albus, L. luteus, and L. mutabilis, are grown as cool-season grain legume crops. Fifteen viruses infect them. Two of these, bean yellow mosaic virus (BYMV) and cucumber mosaic virus (CMV), cause diseases that threaten grain lupin production. Phytosanitary and cultural control measures are mainly used to manage them. However, breeding virus-resistant lupin cultivars provides an additional management approach. The need to develop this approach stimulated a search for virus resistance sources amongst cultivated lupin species and their wild relatives. This review focuses on the progress made in optimizing virus resistance screening procedures, identifying host resistances to BYMV, CMV, and additional viral pathogen alfalfa mosaic virus (AMV), and the inclusion of BYMV and CMV resistance within lupin breeding programs. The resistance types found in different combinations of virus and grain lupin species include localized hypersensitivity, systemic hypersensitivity, extreme resistance, and partial resistance to aphid or seed transmission. These resistances provide a key enabler towards fast tracking gains in grain lupin breeding. Where studied, their inheritance depended upon single dominant genes or was polygenic. Although transgenic virus resistance was incorporated into L. angustifolius and L. luteus successfully, it proved unstable. Priorities for future research are discussed.


The species-specific egg receptor for sea urchin sperm adhesion is EBR1,a novel ADAMTS protein.
Species-specific adhesion of sperm to the egg during sea urchin fertilization involves the interaction of the sperm adhesive protein,bindin, and a complementary receptor on the egg surface,and serves to restrict the gene pool to individuals of the same species. We used PCR representation difference analysis to clone the species-specific egg receptor for bindin, EBR1, from Strongylocentrotus franciscanus (Sf) and S. purpuratus (Sp). Sf-EBR1 contains a novel ADAMTS-like N-terminal domain followed by approximately 19 tandem EBR repeats consisting of alternating CUB and thrombospondin type 1 (TSP-1) domains where the last 10 EBR repeats are species-specific and highly conserved. Recombinant protein corresponding to the species-specific EBR repeat displays species-specific sperm adhesion and bindin-binding activity. The Sp-EBR1 ortholog has the same ADAMTS (a disintegrin and metalloprotease with thrombospondin type-1 modules) core region followed by eight and one-half tandem egg bindin receptor (EBR) repeats that share 88% identity with the Sf-EBR1 repeats,but has an entirely different species-specific domain consisting of hyalin-like (HYR) repeats. Thus,the species-specific domains of egg bindin receptor 1 (EBR1) from both species function as the egg surface receptor to mediate species-specific sperm adhesion.


Closed Incisional Negative Pressure Wound Therapy at Flap Suture Line: An Innovative Approach for Improving Outcomes in Suboptimal Wound Conditions.
Background Persistent dead space following flap cover is a frequently encountered challenge following the reconstruction of complex wounds. It may lead to a hematoma, seroma, wound infection, and wound dehiscence. Wound dehiscence could be a devastating complication. Closed incisional negative pressure wound therapy (ciNPWT) over the surgical incisions was found to reduce surgical site infection (SSI) and wound dehiscence. We applied this principle at the closed flap suture line and through this article, we share the indications, technique, and outcomes. Methods A retrospective analysis (January 2018-June 2019), in which selected high-risk patients who underwent ciNPWT at the flap suture following complex reconstruction (pedicled or free flap) were included in the study. The indications include deep incisional/organ SSI after debridement and flap coverage, persistent dead space following flap coverage, chronic osteomyelitis. Patients were analyzed in the follow-up period in terms of complications, wound healing. Results Nine patients underwent ciNPWT over the flap suture line. The mean age was 32.2 years (range: 10-48 years). The mean duration of the NPWT application was 7.3 days (range: 3-21 days). Three of the nine patients had flap-related minor complications. One patient had marginal flap necrosis and required skin grafting, one patient had minor wound dehiscence (1 cm) which required secondary skin suturing and one patient had chronic discharging sinus related to osteomyelitis of ischium, which subsequently healed with antibiotics and local wound care. None of the patients had NPWT-related complications. Conclusion Closed incisional NPWT decreases the untoward effects of dead space following the reconstruction of complex wounds. The incidence of SSI and wound gaping can be reduced.


A Randomized Controlled Trial on the Efficacy of Integrated Yoga on Pregnancy Outcome.
Physiological and biochemical changes occur in pregnancy to nurture the developing fetus. Pregnancy-related experience is unique to every woman. Pregnancy symptoms and complications can range from mild to severe. Many women can lower their risk by performing different therapies. In this context, the present study targets to evaluate the efficacy of integrated yoga consisting of (asanas and pranayama) on pregnancy to reduce the risk of complications. This study is a prospective randomized controlled single-blinded trial with parallel arms: the intervention arm received specific integrated yoga therapy; the control arm received routine standard care from 18 to 22 weeks of gestation until delivery. The incidence of preeclampsia and preterm delivery was lower in the intervention arm. Women in the intervention arm delivered at higher gestational age. Apgar scores and birth weights of neonates were significantly higher in the intervention arm. The findings suggest that yoga is a safe and effective intervention during pregnancy to reduce or prevent pregnancy-related complications. However, further randomized controlled trials are needed to provide firmer evidence regarding the utility and validity of yoga intervention during pregnancy.


Multi-environment genomic prediction for soluble solids content in peach (Prunus persica).
Genotype-by-environment interaction (G × E) is a common phenomenon influencing genetic improvement in plants, and a good understanding of this phenomenon is important for breeding and cultivar deployment strategies. However, there is little information on G × E in horticultural tree crops, mostly due to evaluation costs, leading to a focus on the development and deployment of locally adapted germplasm. Using sweetness (measured as soluble solids content, SSC) in peach/nectarine assessed at four trials from three US peach-breeding programs as a case study, we evaluated the hypotheses that (i) complex data from multiple breeding programs can be connected using GBLUP models to improve the knowledge of G × E for breeding and deployment and (ii) accounting for a known large-effect quantitative trait locus (QTL) improves the prediction accuracy. Following a structured strategy using univariate and multivariate models containing additive and dominance genomic effects on SSC, a model that included a previously detected QTL and background genomic effects was a significantly better fit than a genome-wide model with completely anonymous markers. Estimates of an individual's narrow-sense and broad-sense heritability for SSC were high (0.57-0.73 and 0.66-0.80, respectively), with 19-32% of total genomic variance explained by the QTL. Genome-wide dominance effects and QTL effects were stable across environments. Significant G × E was detected for background genome effects, mostly due to the low correlation of these effects across seasons within a particular trial. The expected prediction accuracy, estimated from the linear model, was higher than the realised prediction accuracy estimated by cross-validation, suggesting that these two parameters measure different qualities of the prediction models. While prediction accuracy was improved in some cases by combining data across trials, particularly when phenotypic data for untested individuals were available from other trials, this improvement was not consistent. This study confirms that complex data can be combined into a single analysis using GBLUP methods to improve understanding of G × E and also incorporate known QTL effects. In addition, the study generated baseline information to account for population structure in genomic prediction models in horticultural crop improvement.


Use of teriparatide off-label: our experience and review of literature.
The aim of this paper is to report our experience and to present a review of literature about the use of teriparatide off-label in the therapy of non-unions. Teriparatide is used exclusively in treatment of osteoporosis and to prevent bone fracture because it has a positive effect on bone strength and architecture. The use of teriparatide in non-unions is described as effective in numerous case report.


Clot in Lung, Clot in Heart: A Case Report of Tumor-Like Thrombus in Right Atrium.
Tumor-like formation of thrombus in the right atrial cavity is rare. It may be mistaken for a myxoma. The exact pathophysiology of an isolated thrombus in the heart is still unclear. Management to prevent complications such as pulmonary thromboembolism depends on the clinical judgment of a cardiologist. This report describes a 76-year-old woman with right atrial thrombus causing subsequent pulmonary thromboembolism in right lung. She initially presented to us with pulmonary embolism, and later, an incidental finding of a mass in her right atrium revealed an association of thrombus in heart with thrombus in lung. The challenging management was to resect this thrombus which was fixed to atrial septum, and a trial of anticoagulation did not resolve it. Exact management of such incidental findings in right heart cavities is not well established. Some cases may benefit from resection of such formed fixed thrombus.


Associations of youth and parent weight status with reported versus predicted daily energy intake and hemoglobin A1c in youth with type 1 diabetes mellitus.
The epidemic of overweight/obesity affects youth with type 1 diabetes mellitus (T1DM) and their families. In youth with T1DM and their parents, we examined weight status with reported and expected energy intake and with youth hemoglobin A1c (HbA1c). In 243 youth (48% female, 13 ± 3 years) and their parents (84% female, 45 ± 6 years), we assessed body mass index (BMI), prevalence of overweight/obesity, reported energy intake (REI), and youth glycemic control (HbA1c). The REI was compared with predicted daily energy requirements (DER; based on age, weight, sex, and physical activity). Youth had diabetes duration of 6.3 ± 3.4 years and HbA1c of 8.5% ± 1.3%; 69% used insulin pump therapy. Overweight and obesity affected 23% and 11% of youth and 30% and 24% of parents, respectively. Youth and parent BMI (r = 0.38; p < .001) and weight status (overweight/obese; p < .001) were significantly associated. The ratio of REI:DER was significantly lower in overweight/obese compared with underweight/normal weight parents (1.0 ± 0.4 versus 1.2 ± 0.5; p = .001) but did not differ among youth by weight status. Both youth and parent BMI were positively correlated with youth HbA1c (r = 0.14, p = .02; r = 0.16, p = .01, respectively). Hemoglobin A1c tended to be higher in obese than in overweight and normal weight youth (mean ± standard deviation [SD] 8.4 ± 1.4, 8.4 ± 1.3, and 8.8 ± 1.0, respectively; p = .06) and was significantly higher in youth whose parents were obese versus overweight or underweight/normal weight (mean ± SD 8.2 ± 1.2, 8.5 ± 1.4, and 8.9 ± 1.5, respectively; p < .001). Similar to the general population, overweight and obesity are prevalent among families of youth with T1DM. Weight status appears to influence self-REI in parents and glycemic control in youth with T1DM, suggesting the need for family-based dietary interventions.


Metabolic rate increases with acclimation temperature and is associated with mitochondrial function in some tissues of threespine stickleback.
The metabolic rate (ṀO2) of eurythermal fishes changes in response to temperature, yet it is unclear how changes in mitochondrial function contribute to changes in ṀO2. We hypothesized that ṀO2 would increase with acclimation temperature in the threespine stickleback (Gasterosteus aculeatus) in parallel with metabolic remodeling at the cellular level but that changes in metabolism in some tissues, such as liver, would contribute more to changes in ṀO2 than others. Threespine stickleback were acclimated to 5, 12 and 20°C for 7 to 21 weeks. At each temperature, standard and maximum metabolic rate (SMR and MMR, respectively), and absolute aerobic scope (AAS) were quantified, along with mitochondrial respiration rates in liver, oxidative skeletal and cardiac muscles, and the maximal activity of citrate synthase (CS) and lactate dehydrogenase (LDH) in liver, and oxidative and glycolytic skeletal muscles. SMR, MMR and AAS increased with acclimation temperature, along with rates of mitochondrial phosphorylating respiration in all tissues. Low SMR and MMR at 5°C were associated with low or undetectable rates of mitochondrial complex II activity and a greater reliance on complex I activity in liver, oxidative skeletal muscle and heart. SMR was positively correlated with cytochrome c oxidase (CCO) activity in liver and oxidative muscle, but not mitochondrial proton leak, whereas MMR was positively correlated with CCO activity in liver. Overall, the results suggest that changes in ṀO2 in response to temperature are driven by changes in some aspects of mitochondrial function in some, but not all, tissues of threespine stickleback.


The reconstruction of the pilot in command murder case in the aircraft OK ADN L410 Turbolet.
The aim of this paper is to reconstruct the hijacking case of an aircraft on the Mariánské Lázně - Prague route in 1972 and the shooting of its pilot in command in light of new facts, mainly autopsy reports from both Germany and Czechoslovak Socialist Republic. These reports contained absolutely opposite findings, both in terms of the findings themselves and their resulting interpretations. Since it is still not yet known exactly what happened in the plane, a reconstruction was carried out in an identical aircraft in the Aviation Museum in Kunovice. During the reconstruction, all possible (including theoretical) situations that may have occurred in the aircraft were examined. It was found that this could not have been a premeditated intentional murder, but that the shot could only have occurred during a passenger skirmish, and one that must have resulted in a very rare situation at that. From a political-medical point of view however, there are still several questions that cannot be answered even with the best of intentions.


Separate and Joint Associations of Remnant Cholesterol Accumulation and Variability With Carotid Atherosclerosis: A Prospective Cohort Study.
Background We aimed to examine separate and joint associations of remnant cholesterol (RC) accumulation and variability with the risk of carotid atherosclerosis (CAS) in the general population. Methods and Results A total of 6213 participants who underwent 3 sequential health examinations during 2010 to 2015 were enrolled and were followed up until December 31, 2021. Cumulative RC (cumRC) and RC variability among the 3 visits were the exposure of interest in our study. Adjusted Cox models were performed to calculate the hazard ratio (HR) and 95% CI. C-statistics, integrated discrimination improvement, and the net reclassification index were used to estimate the incremental predictive ability. During a median follow-up of 4.00 years, 2613 participants developed CAS. Higher cumRC (HR, 1.33 [95% CI, 1.17-1.52]) and greater RC variability (HR, 1.22 [95% CI, 1.08-1.39]) were significantly associated with elevated risk of CAS, independent of traditional cardiovascular risk factors and low-density lipoprotein cholesterol. Participants were divided into 4 groups according to the median of cumRC and RC variability to assess their joint associations. Compared with "low cumRC and low variability," "high cumRC and high variability" had the highest risk of CAS, followed by "high cumRC and low variability" and "low cumRC and high variability." Finally, joint assessment of RC accumulation and variability had the significantly highest incremental effect on the predictive value of CAS versus single-time-point measures of RC. Conclusions Excessive cumRC levels and greater RC variability were each independently associated with higher incidence of CAS, and their coexistence could further yield significantly higher risks.


Influence of Hospital Volume Effects and Minimum Caseload Requirements on Quality of Care in Pancreatic Surgery in Germany.
Numerous international studies have identified hospital volume as significant independent variable of death following pancreatic surgery. Most of these studies were limited to regions of countries or portions of a national population and did not include data on volume-outcome effects in Germany. The Medline database was systematically searched to identify studies that analyzed volume-outcome relationships and effects of minimum caseload requirements on outcomes of pancreatic surgery in Germany. Recent observational studies utilizing German hospital discharge data confirmed that patients undergoing pancreatic surgery in Germany also have better outcomes when treated in facilities with high annual caseloads. Besides a decreased risk of in-hospital mortality, there is also a reduced risk of 1-year mortality in high-volume hospitals. In addition, there is evidence that adherence to already existing minimum caseload requirements reduces morbidity and mortality of pancreatic surgery in Germany. As a result of an insufficient centralization in the recent past, however, a large proportion of hospitals that perform pancreatic surgery still do not meet minimum caseload requirements. Specific measures (i.e. sanctions for failure to achieve minimum volumes) that initiate a sufficient centralization process without threatening patient access to surgical care are needed.